The blood–brain barrier and blood–tumour barrier in brain tumours and metastases

Arvanitis, Costas D.; Ferraro, Gino B.; Jain, Rakesh K.

doi:10.1038/s41568-019-0205-x

Cited by 994 publications

(826 citation statements)

References 227 publications

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“…Glioma heterogeneity is reflected in the variable amount of BBB preservation across WHO grades and also in the very same histotype [31]. Thus, in human specimens of glioma (WHO grade II to IV), we assessed tumor areas with various degrees of BBB disruption, as revealed by the amount of Gd enhancement on MR, that were targeted intraoperatively by navigational systems.…”

Section: Discussionmentioning

confidence: 99%

Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood–Brain Barrier

Pacioni

D’Alessandris

Buccarelli

et al. 2019

Cancers

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The question whether perivascular glioma cells invading the brain far from the tumor bulk may disrupt the blood-brain barrier (BBB) represents a crucial issue because under this condition tumor cells would be no more protected from the reach of chemotherapeutic drugs. A recent in vivo study that used human xenolines, demonstrated that single glioma cells migrating away from the tumor bulk are sufficient to breach the BBB. Here, we used brain xenografts of patient-derived glioma stem-like cells (GSCs) to show by immunostaining that in spite of massive perivascular invasion, BBB integrity was preserved in the majority of vessels located outside the tumor bulk. Interestingly, the tumor cells that invaded the brain for the longest distances traveled along vessels with retained BBB integrity. In surgical specimens of malignant glioma, the area of brain invasion showed several vessels with preserved BBB that were surrounded by tumor cells. On transmission electron microscopy, the cell inter-junctions and basal lamina of the brain endothelium were preserved even in conditions in which the tumor cells lay adjacently to blood vessels. In conclusion, BBB integrity associates with extensive perivascular invasion of glioma cells.

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Section: Discussionmentioning

confidence: 99%

Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood–Brain Barrier

Pacioni

D’Alessandris

Buccarelli

et al. 2019

Cancers

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“…In particular, animal studies would allow more complex protocols, which could be applied to investigate animal models of BBB disorders. 37 Another promising approach would be to apply the method in patients with a known BBB dysfunction such as brain tumors, 38 or to induce temporary BBB permeability change in healthy subjects with transcranial magnetic stimulation. 39 With regard to future clinical applications, a shorter scan protocol would be required.…”

Section: Discussionmentioning

confidence: 99%

Blood–brain barrier permeability measurement by biexponentially modeling whole‐brain arterial spin labeling data with multiple T₂‐weightings

et al. 2020

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Blood–brain barrier (BBB) permeability assessment remains of ongoing interest in clinical practice and research. Transitions between intravascular (IV) and extravascular (EV) gray matter (GM) compartments may provide information regarding the microstructural status of the BBB. Due to different transverse relaxation times (T2) of water protons in vessels and GM, it is possible to determine the compartment in which these protons are located. This work presents and investigates the feasibility of a simplified analytical approach for compartmentalizing the proportions of magnetically marked water protons into IV and EV GM components by biexponentially modeling T2‐weighted arterial spin labeling (ASL) data. Numerous model assumptions were used to stabilize the fit and achieve in vivo applicability. Particularly, transverse relaxation times of IV and EV water protons were determined from the analysis of two supporting T2‐weighted ASL measurements, utilizing a monoexponential signal model. This stabilized a two‐parameter biexponential fit of ASL data with T2 preparation (PLD = 0.9/1.2/1.5/1.8 s, TET2Prep = 0/30/40/60/80/120/160 ms), which thereby robustly provided estimates of the IV and EV compartment fractions. Experiments were conducted with three healthy volunteers in a 3 T scanner. Averaged over all subjects, the labeled water protons inherit T2,IV = 200 ± 18 ms initially and adapt T2,EV = 91 ± 2 ms with a longer retention time in cerebral structures. Accordingly, the EVlocated ASL signal fraction rises with increasing PLD from 0.31 ± 0.11 at the shortest PLD of 0.9 s to 0.73 ± 0.02 at the longest PLD of 1.8s. These results indicate a transition of the water protons from IV to EV space. The findings support the potential of biexponential modeling for compartmentalizing ASL spin fractions between IV and EV space. The novel integration of monoexponential parameter estimates stabilizes the two‐compartment model fit, suggesting that this technique is suitable for robustly estimating the BBB permeability in vivo.

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“…Systemic treatment is of growing importance in the treatment of patients with metastatic disease. Even BM, which for a long time were not considered susceptible to systemic treatment due to them blood-brainbarrier, have been shown to be regressive under new systemic agents [32]. The best intracranial control seems to be achieved with a combination of immunotherapy and radiosurgery while not having a signi cantly higher rates of RN [33].…”

Section: Discussionmentioning

confidence: 99%

Simultaneous stereotactic radiosurgery of multiple brain metastases using single isocenter dynamic conformal arc therapy: a prospective monocentric registry trial

Bodensohn

Kaempfel

Fleischmann

et al. 2020

Preprint

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Background Single-isocenter dynamic conformal arc (SIDCA) therapy is an efficient way of delivering stereotactic radiosurgery (SRS) to multiple metastases simultaneously. This study reports on the safety and feasibility of SRS with SIDCA for patients with multiple brain metastases.Methods All patients who received SRS with this technique between November 2017 and June 2019 within a prospective registry trial, were included. The patients were irradiated using a VersaHD® linear accelerator (LINAC) from Elekta (Stockholm, Sweden). Follow-up was performed every three months, including a clinical and radiological examination with cranial magnetic resonance imaging (MRI). The data were analyzed using descriptive statistics and the Kaplan-Meier method.Results 65 patients with 254 lesions (range 2–12) were included in this analysis. Median beam on time was 23 minutes. The median follow-up at the time of analysis was 13 months (95% CI 11.1–14.9). Median overall survival and median progression-free survival was 15 months (95% CI 7.7–22.3) and 18 months (95% CI 11.1–24.9), respectively. Intracranial and local control after 6 months was 73.0% and 97.5%, respectively. During follow-up, CTCAE grade 1 adverse effects (AE) were experienced by 29 (44.6%) patients (18 of them therapy-related (27.7%)), CTCAE grade 2 AEs by 4 (6.2%) patients (one of them therapy-related (1.5%)) and CTCAE grade 3 by 3 patients (4.6%) (none of them therapy-related). 2 lesions (0.8%) in 2 patients (3.1%) were proven as radiation necrosis. Conclusions Simultaneous SRS using SIDCA seems to be a feasible and safe treatment for patients with multiple metastases.

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The blood–brain barrier and blood–tumour barrier in brain tumours and metastases

Cited by 994 publications

References 227 publications

Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood–Brain Barrier

Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood–Brain Barrier

Blood–brain barrier permeability measurement by biexponentially modeling whole‐brain arterial spin labeling data with multiple T₂‐weightings

Simultaneous stereotactic radiosurgery of multiple brain metastases using single isocenter dynamic conformal arc therapy: a prospective monocentric registry trial

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The blood–brain barrier and blood–tumour barrier in brain tumours and metastases

Cited by 994 publications

References 227 publications

Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood–Brain Barrier

Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood–Brain Barrier

Blood–brain barrier permeability measurement by biexponentially modeling whole‐brain arterial spin labeling data with multiple T2‐weightings

Simultaneous stereotactic radiosurgery of multiple brain metastases using single isocenter dynamic conformal arc therapy: a prospective monocentric registry trial

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Blood–brain barrier permeability measurement by biexponentially modeling whole‐brain arterial spin labeling data with multiple T₂‐weightings